Integrative transcriptomics and metabolomics analyses provide hepatotoxicity mechanisms of asarum

Abstract

Asarum is frequently applied in combination with other agents for prescriptions in practices of Traditional Chinese Medicine. A number of studies have previously indicated that asarum treatment induces lung toxicity by triggering inflammation. However, the potential effects of asarum in the liver and the underlying mechanisms have remained largely elusive. Therefore, transcriptomics and metabolomics approaches were used in the present study to examine the mechanisms of the hepatotoxicity of asarum. Specifically, mRNA and metabolites were obtained from rat liver samples following intragastric administration of asarum powder. RNA sequencing analysis was subsequently performed to screen for differentially expressed genes (DEGs), and a total of 434 DEGs were identified in liver tissue samples, 214 of which were upregulated and 220 were downregulated. Pathway enrichment analysis found that these genes were particularly enriched in processes including the regulation of p53 signaling, metabolic pathways and bile secretion. To investigate potential changes to the metabolic profile as a result of asarum treatment, a metabolomics analysis was performed, which detected 14 significantly altered metabolites in rat liver samples by gas chromatography-mass spectrometry. These metabolites were predominantly members of the taurine, hypotaurine and amino acid metabolic pathways. Metscape network analyses were subsequently performed to integrate the transcriptomics and metabolomics data. Integrative analyis revealed that the DEGs and metabolites were primarily associated with bile acid biosynthesis, amino acid metabolism and the p53 signaling pathway. Taken together, these results provide novel insight into the mechanism of asarum-mediated hepatotoxicity, which may potentially aid the clinical diagnosis and future therapeutic intervention of asarum poisoning.